Various hereditary, acquired and neoplastic conditions can lead to cyst formation in the kidney.
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1 Dr. Fatima AlAl-Hashimi Hashimi,, MD, FRCPath Salmaniya Medical Complex, Bahrain
2 Various hereditary, acquired and neoplastic conditions can lead to cyst formation in the kidney. The most frequently encountered form of renal cystic lesion is the unilocular, simple, renal cortical cyst Others can appear on imaging as solitary or multiple, complex cystic lesions, with variable likelihood of being malignant neoplasms. Cystic lesions of the kidney Hereditary cysts and Potential Preneoplastic Lesions Cystic Neoplasms
3 Acquired Cystic Disease o ACD-Associated RCC o Clear Cell Papillary RCC von of the kidney Hippel-Lindau Syndrome Tuberous Sclerosis Complex Autosomal-Dominant Polycystic Kidney Disease Other cysts with or without associated Tumours
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5 Incidence of developing RCC in patients with ACDK is 3-7%, that represents up to 100 times greater risk than the general population The duration of dialysis correlates (ESRD) with the incidence of ACDK and RCC The tumour types seen in ESRD and ACDK encompass: o Three common subtypes of RCC, including: Clear Cell RCC, papillary RCC and Chromophobe RCC o The two other types are predominantly seen in ESRD: acquired cystic (ACD)-associated RCC and clear cell papillary RCC
6 ACD-associated RCC is the most common subtype of RCC seen in ACDK, accounting for the dominant mass in 36% of end-stage kidneys overall and in 46% ACDK The tumour shows various combinations of acinar, solid alveolar, solid, microcystic and papillary architecture The prominent papillary architecture may lead to misinterpretation as type 2 papillary RCC Positive for AE1/3, CD10, RCC-Ag, and AMACR. Negative or focal for CK7. Tumour cells usually have abundant granular, eosinophilic cytoplasm and large nuclei with prominent nucleoli. Intracytoplasmic and intercellular lumina, imparting a cribriform or sievelike appearance. Exclusively have intratumoral oxalate crystals.
7 2nd most common subtype of RCC in ESRD CCP-RCC is composed of various proportions of papillary, tubular, cystic and solid or nested architectures with clear cytoplasm Small blunt papillae, focal branching papillae and interconnecting ribbon are common. However, extensively branching papillae are uncommon Low-grade (Fuhrman grade 1 2) nuclei Most characteristic features is the linear arrangement of the tumor nuclei away from the basal aspects of the cells, either in the middle of the cell or closer to the apex Foamy macrophages, tumor necrosis, and vascular invasion are not a feature Cup shaped staining for CA-IX. CK7 positive. AMACR and CD10 negative
8 The biologic behaviour of RCCs in ESRD is reported to be less aggressive than that of the RCCs in sporadic or non-esrd settings The tumours, are often smaller and at lower stage. However, a few cases have behaved aggressively and metastasized ACD-associated RCC may have a greater potential for aggressive behavior than do other types of tumours in ESRD Rare cases with sarcomatoid features have been reported, and as would be expected, these cases show aggressive clinical behaviour
9 Autosomal dominant, deletion of gene located on 3p25-26
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11 Benign cyst, lined by a one-cell thick lining The cysts from patients with VHL disease are multiple, bilateral, and lined exclusively by clear cells. Atypical cyst, 2-3 cells thick with focal papillary tufting
12 RCC is often multicenteric and bilateral. In patients with VHL germline mutation, deletion of the second VHL allele is associated with overexpression of CAIX. Whether histologically designated as benign or atypical, the cysts lined by clear cells, or even single renal renal tubular epithelial cells with the VHL gene deletion likely present precursor lesions for CCRCC Almost all tumours in the VHL setting are clear cell RCCs of low nuclear grade (Fuhrman grade 1/2). The RCCs have often multicenteric and bilateral, arising both in cysts and de novo from noncystic renal parenchyma As RCCs continue to develop in both kidneys, clinical maanagemet relies on a delicate balance between excising tumours (>3cm) to prevent mets and preserving renal tissue
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14 Autosomal dominant, hereditary disease. Underlying molecular alterations are inactivating mutations of TSC1 or TSC2, tumour suppressor genes on chromosome arm 9q and 16p encoding hamartin and tuberin, respectively.
15 Renal cysts occur in 30-40% of cases. Usually small and scattered within an otherwise unremarkable, intervening renal parenchyma Typical cysts of TSC are lined by granular eosinophilic cells with large nuclei; some cysts show papillary tufting or intraluminal papillary excrescences filling the cyst Angiomyolipomas involve 50% to 100% of patients and often bilateral and multifocal. The rare variant, epithelioid AML, is reported more frequently in TSC than in patients without TSC.
16 CCRR is reported to be the most frequent type Other tumours include renal oncocytomas, chromophobe RCC, Or unclassified tumours composed of large cells with pink granular cytoplasm Recently, some TSC-associated RCCs mimicking translocation-associated carcinomas were described. These were negative for TFE on immunohistochemistry.
17 The cyst lesions in TSC can vary from scattered, occasional cysts to numerous cysts, imparting a spongelike appearance. The classic cysts in TSC are lined by granular eosinophilic cells with large nuclei A tumor from a young patient with TSC composed of cells with abundant, eosinophilic, granular cytoplasm. The periphery of the tumor exhibits the papillary architectural pattern with prominent, foamy histiocytes filling up the fibrovascular cores. Additional tumors resected from the same patient show prominent, papillary architecture and cells with voluminous clear cytoplasm and high nuclear grade, mimicking translocation-associated renal cell carcinoma. TFE3 and TFEB immunostains are negative in such tumors.
18 TSC-associated papillary RCC. The have a nucleolar grade 2 or 3 with mostly basally located nuclei. TSCassociated PRCC show strong, diffuse labeling for CA-IX (100%), CK7 (94%), vimentin (88%), CD10 (83%), and are uniformly negative for succinate dehydrogenase subunit B (SDHB), TFE3 and AMACR.
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20 Multilocular Cystic RCC Cystic Nephroma and Mixed Epithelial and Stromal Tumour Clear Cell Papillary RCC Tubulocystic Carcinoma of the kidney Intrinsic Cystic Formation in Other Renal Cell Tumours of Various Subtypes RCC with Cystic Necrosis Epithelial Cysts in Mesenchymal Tumours Likely Developing from Entrapped Renal Tubules
21 Multilocular cystic RCC, a renal cortical neoplasm with a distinct, multilocular gross appearance, is a variant of clear cell RCC. Solid, grossly discernable mural nodules of the tumour are incompatible with the diagnosis The tumour consists of numerous clear cell lined cysts with small clusters of clear cells in the tumour septae. The tumour nuclei are small, uniform and round without prominent nucleoli The cystic tumor is often an incidental finding, and often presents as a unilateral, solitary lesion VHL mutations were identified in 25% of the cases The tumor cells are strongly reactive to PAX2 and CAIX, similar to typical, low-grade clear cell RCC. These findings are consistent with the concept of multilocular cystic RCC being a variant of clear cell RCCs In line with the minimal tumor burden present in these tumors, prognosis is excellent; there was no recurrence or metastases on mean follow-up of more than 6.5 years in a more-recent study
22 An important diagnostic feature is the presence of tumour cells in the fibrous septae similar to those lining the cysts.
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25 Cystic nephroma is entirely cystic, without any solid expansile growth or mural nodules The mixed epithelial and stromal tumor is a multicystic or biphasic tumor with solid and cystic areas In the adult population, both tumors show a marked female preponderance (F:M, 8:1) Steroid hormones have been suggested to play a role in the genesis and evolution of these tumors
26 Cystic nephroma in the pediatric age group is an entity entirely distinct from the adult tumors and is considered a fully differentiated nephroblastoma (Wilms tumor)
27 Well circumscribed, variable sized cystically dilated tubules, cuboidal, atypical eosinophilic/cleared cells, nucleoli, hobnail features, mucinous secretions, absent mitoses. Paucicellular fibrous septa Originally termed low grade collecting duct carcinoma renamed to emphasize distinction from CDC: morphology & indolent behavior (<10% mets) Histogenesis: proximal convoluted tubules vs intercalated cells of collecting ducts. DDX: MEST both sexes, lack of hypercellular/ovarian like stroma, atypical nuclear features, prominent nucleoli IHC : CD10, AMACR, CK 19 & 34βE12.
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29 The presence of multiple renal cysts, both acquired and syndromic, may be associated with a variety of renal tumours. The morphology of the cysts and associated tumour types can help predict the genetic or acquired basis of the lesions, and such potential associations should be suggested in surgical pathology reports.
30 Shukran!
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